Regulation of gut microbiome with redox responsible bacterial cellulose hydrogel for precision chemo-radiotherapy of intestinal cancer

Abstract

Although various types of radiosensitive nanoplatforms are explored to enhance radiotherapy, digestible and radiosensitive nanofiber hydrogel with sensitive responsiveness to the intestinal environment, greatly amplified radiation-induced intestinal tumor destruction, as well as the ability to regulate gut microbiome is still demanded. Herein, sulfhydryl crosslinked bacterial cellulose hydrogel (SulBC gel) was synthesized through silylation and oxidation reaction. Anticancer drug, cis-dichlorodiamineplatinum (CDDP) is loaded into the hydrogel (CDDP@SulBC gel) for precision radiotherapy of intestinal cancer. The CDDP@SulBC gel selectively degrades and consequently exhibits an accelerated drug release behavior in reductive environments. Meanwhile, the CDDP@SulBC gel can increase X-ray-induced double-strand breaks, induce G2/M phase arrest, and enhance the radio-sensitivity to intestinal tumor cells. Upon intragastric administration of CDDP@SulBC gel, the hydrogel is noninvasively monitored in the gastrointestine by micro-CT imaging contributed to the relative high Z-element of silicon and shows an excellent anti-tumor efficacy under X-ray-irradiation of the human intestinal cancer xenograft nude mice. Additionally, the hydrogel can also elevate the ratio of Bacteroidetes / Firmicutes and reconstruct gut microbiome balance, benefiting to the reduction of colitis induced by irradiation. This work thus presents a digestible nanofiber hydrogel-based radiosensitizer with in vivo micro-CT imaging, intestine-specific decomposition/drug release profiles, and great efficacy in chemo-radiotherapy of cancer.